Systematic Review and Meta-Analyses of the Effects of Phosphate-Lowering Agents in Nondialysis CKD

Lioufas, Nicole; Pascoe, Elaine M.; Hawley, Carmel; Elder, Grahame J.; Badve, Sunil V.; Block, Geoffrey A.; Johnson, David W.; Toussaint, Nigel D

doi:10.1681/asn.2021040554

Cited by 20 publications

(12 citation statements)

References 64 publications

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“…Further studies are required to specifically target the nondialysis CKD population, as VC response to therapy may be different in this population compared with patients on dialysis. For example, the safety and efficacy of phosphate binders in nondialysis CKD has been recently called into question, 93 in contrast to the potential benefit of noncalcium-based compared with calcium-based phosphate binders in dialysis patients. 94 Heterogeneity was also seen in trials with regard to baseline VC, study design (randomized and nonrandomized), study duration, VC imaging modality, and VC anatomic site.…”

Section: Discussionmentioning

confidence: 99%

Interventions To Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of Clinical Trials

Smith

Tiong

et al. 2022

JASN

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Background Vascular calcification is associated with cardiovascular morbidity and mortality in people with chronic kidney disease (CKD). Evidence-based interventions that may attenuate its progression in CKD remain uncertain. Methods We conducted a systematic review of prospective clinical trials of interventions to attenuate vascular calcification in people with CKD, compare with placebo, another comparator, or standard of care. We included prospective clinical trials (randomized and nonrandomized) involving participants with stage 3-5D CKD or kidney transplant recipients; the outcome was vascular calcification measured using radiological methods. Quality of evidence was determined by the Cochrane risk of bias assessment tool and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method. Results There were 77 trials (63 randomized) involving 6898 participants eligible for inclusion (median sample size, 50; median duration, 12 months); 58 involved participants on dialysis, 15 involved individuals with nondialysis CKD, and 4 involved kidney transplant recipients. Risk of bias was moderate over all. Trials involving magnesium and sodium thiosulfate consistently showed attenuation of vascular calcification. Trials involving intestinal phosphate binders, alterations in dialysate calcium concentration, vitamin K therapy, calcimimetics, and antiresorptive agents had conflicting or inconclusive outcomes. Trials involving vitamin D therapy and HMG-CoA reductase inhibitors did not demonstrate attenuation of vascular calcification. Mixed results were reported for single studies of exercise, vitamin E-coated or high-flux hemodialysis membranes, interdialytic sodium bicarbonate, SNF472, spironolactone, sotatercept, nicotinamide, and oral activated charcoal. Conclusions Currently, there are insufficient or conflicting data regarding interventions evaluated in clinical trials for mitigation of vascular calcification in people with CKD. Therapy involving magnesium or sodium thiosulfate appears most promising, but evaluable studies were small and of short duration.

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Section: Discussionmentioning

confidence: 99%

Interventions To Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of Clinical Trials

Smith

Tiong

et al. 2022

JASN

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“…Elevated serum phosphate levels lead to vascular calcification and are associated with an increased risk of cardiovascular events and mortality in patients with CKD, although the benefits of phosphate-lowering therapies on clinical outcomes remain uncertain [ 50 ]. Because plant phosphorus is bound to phytates, which are difficult for humans to digest, it is much less bioavailable than animal phosphorus and inorganic phosphorus in food additives.…”

Section: Benefits Of a Plant-based Diet For Patients With Ckdmentioning

confidence: 99%

Plant-Dominant Low Protein Diet: A Potential Alternative Dietary Practice for Patients with Chronic Kidney Disease

2023

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Dietary protein restriction has long been a cornerstone of nutritional therapy for patients with chronic kidney diseases (CKD). However, the recommended amount of dietary protein intake is different across guidelines. This is partly because previous randomized controlled trials have reported conflicting results regarding the efficacy of protein restriction in terms of kidney outcomes. Interestingly, a vegetarian, very low protein diet has been shown to reduce the risk of kidney failure among patients with advanced CKD, without increasing the incidence of hyperkalemia. This finding suggests that the source of protein may also influence the kidney outcomes. Furthermore, a plant-dominant low-protein diet (PLADO) has recently been proposed as an alternative dietary therapy for patients with CKD. There are several potential mechanisms by which plant-based diets would benefit patients with CKD. For example, plant-based diets may reduce the production of gut-derived uremic toxins by increasing the intake of fiber, and are useful for correcting metabolic acidosis and hyperphosphatemia. Plant proteins are less likely to induce glomerular hyperfiltration than animal proteins. Furthermore, plant-based diets increase magnesium intake, which may prevent vascular calcification. More evidence is needed to establish the efficacy, safety, and feasibility of PLADO as a new adjunct therapy in real-world patients with CKD.

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“…To date, phosphate binders are the only approved pharmacological treatment for hyperphosphatemia. Phosphate control is accomplished primarily through calcium-free phosphate binders [ 14 ]. However, any additional improvements in clinical cardiovascular outcomes still remain elusive [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Magnesium Improves Cardiac Function in Experimental Uremia by Altering Cardiac Elastin Protein Content

et al. 2023

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Cardiovascular complications are accompanied by life-threatening complications and represent the major cause of death in patients with chronic kidney disease (CKD). Magnesium is important for the physiology of cardiac function, and its deficiency is common in CKD. In the present study, we investigated the impact of oral magnesium carbonate supplementation on cardiac function in an experimental model of CKD induced in Wistar rats by an adenine diet. Echocardiographic analyses revealed restoration of impaired left ventricular cardiac function in animals with CKD. Cardiac histology and real-time PCR confirmed a high amount of elastin protein and increased collagen III expression in CKD rats supplemented with dietary magnesium as compared with CKD controls. Both structural proteins are crucial in maintaining cardiac health and physiology. Aortic calcium content increased in CKD as compared with tissue from control animals. Magnesium supplementation numerically lowered the increases in aortic calcium content as it remained statistically unchanged, compared with controls. In summary, the present study provides evidence for an improvement in cardiovascular function and aortic wall integrity in a rat model of CKD by magnesium, as evidenced by echocardiography and histology.

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Systematic Review and Meta-Analyses of the Effects of Phosphate-Lowering Agents in Nondialysis CKD

Cited by 20 publications

References 64 publications

Interventions To Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of Clinical Trials

Interventions To Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of Clinical Trials

Plant-Dominant Low Protein Diet: A Potential Alternative Dietary Practice for Patients with Chronic Kidney Disease

Magnesium Improves Cardiac Function in Experimental Uremia by Altering Cardiac Elastin Protein Content

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